Cambridge Infectious Diseases Consortium, Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
PLoS Pathog. 2012;8(5):e1002730. doi: 10.1371/journal.ppat.1002730. Epub 2012 May 31.
Influenza viruses are characterized by an ability to cross species boundaries and evade host immunity, sometimes with devastating consequences. The 2009 pandemic of H1N1 influenza A virus highlights the importance of pigs in influenza emergence, particularly as intermediate hosts by which avian viruses adapt to mammals before emerging in humans. Although segment reassortment has commonly been associated with influenza emergence, an expanded host-range is also likely to be associated with the accumulation of specific beneficial point mutations. To better understand the mechanisms that shape the genetic diversity of avian-like viruses in pigs, we studied the evolutionary dynamics of an Eurasian Avian-like swine influenza virus (EA-SIV) in naïve and vaccinated pigs linked by natural transmission. We analyzed multiple clones of the hemagglutinin 1 (HA1) gene derived from consecutive daily viral populations. Strikingly, we observed both transient and fixed changes in the consensus sequence along the transmission chain. Hence, the mutational spectrum of intra-host EA-SIV populations is highly dynamic and allele fixation can occur with extreme rapidity. In addition, mutations that could potentially alter host-range and antigenicity were transmitted between animals and mixed infections were commonplace, even in vaccinated pigs. Finally, we repeatedly detected distinct stop codons in virus samples from co-housed pigs, suggesting that they persisted within hosts and were transmitted among them. This implies that mutations that reduce viral fitness in one host, but which could lead to fitness benefits in a novel host, can circulate at low frequencies.
流感病毒的特点是能够跨越物种界限并逃避宿主免疫，有时会造成毁灭性的后果。2009 年的甲型 H1N1 流感大流行突出了猪在流感出现中的重要性，特别是作为中间宿主，禽病毒通过它适应哺乳动物，然后在人类中出现。尽管片段重配通常与流感的出现有关，但扩大宿主范围也可能与特定有益的点突变的积累有关。为了更好地了解塑造猪中类似禽的病毒遗传多样性的机制，我们研究了通过自然传播联系在一起的未接种疫苗和接种疫苗的猪中欧亚类禽猪流感病毒（EA-SIV）的进化动态。我们分析了来自连续日病毒群的多个血凝素 1（HA1）基因克隆。引人注目的是，我们在传播链中观察到了共识序列的瞬时和固定变化。因此，宿主内 EA-SIV 群体的突变谱是高度动态的，等位基因固定可以极快地发生。此外，能够改变宿主范围和抗原性的突变在动物之间传播，混合感染很常见，即使在接种疫苗的猪中也是如此。最后，我们在共同饲养的猪的病毒样本中反复检测到不同的终止密码子，表明它们在宿主内持续存在并在宿主之间传播。这意味着在一个宿主中降低病毒适应性但可能导致新宿主适应性增强的突变可以以低频率传播。
